The present review addresses the most recent literature regarding the diagnosis of drug hypersensitivity reactions, which can be classified as immediate or nonimmediate according to the time interval between the last drug administration and the onset. Immediate reactions occur within 1 h; nonimmediate ones occur after more than 1 h. Clinical and immunological studies suggest that type-I (IgE-mediated) and type-IV (cell-mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. New diagnostic tools, such as the basophil activation test and the lymphocyte activation test, have been developed and are under validation. In diagnosis, the patient's history is fundamental; the allergologic examination includes in-vivo and in-vitro tests selected on the basis of the clinical features. Prick, patch, and intradermal tests are the most readily available forms of allergy testing. Determination of specific IgE levels is still the most common in-vitro method for diagnosing immediate reactions. The sensitivity of allergologic tests is not 100%; in selected cases, therefore, provocation tests are necessary. The routine use of the basophil activation test and the lymphocyte activation test could increase the sensitivity of diagnostic work-ups, thus reducing the need for drug provocation tests.